A Study of CD19 Targeted CAR T Cell Therapy in Patients With Severe, Refractory Systemic Lupus Erythematosus (SLE) (CARLYSE)

A Single-Arm, Open-Label, Phase I Study to Determine the Safety, Tolerability and Preliminary Efficacy of Obecabtagene Autoleucel in Patients With Severe, Refractory Systemic Lupus Erythematosus

This is a Phase I study of obecabtagene autoleucel (obe-cel), autologous T cells engineered with a chimeric antigen receptor (CAR) targeting CD19, to establish the tolerability, safety, preliminary efficacy, and pharmacokinetics of obe-cel in patients with severe, refractory SLE.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: Obecabtagene autoleucel (obe-cel)

Detailed Description

This is a single-arm, open-label Phase I Study to determine the safety, tolerability, and preliminary efficacy of obe-cel in patients with severe, refractory SLE. A maximum of n=12 patients will be treated in a maximum of 3 dose levels.

By using the Bayesian Optimal Interval (BOIN) design for overdose control, the Sponsor will review the Safety Review Committee (SRC) and Independent Data Monitoring Committee (IDMC) recommendation and determine if a dose level is suitable for a subsequent study.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Autolus Limited; Phone Number: +44 (0) 203 911 4385; Email: clinicaltrials@autolus.com

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • University College London Hospitals NHS Foundation Trust
    • Contact: Maria Leandro; Email: uclh.car-ttrials@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

-Key Inclusion Criteria-

• Diagnosis of SLE fulfilling the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria for Systemic Lupus Erythematosus
• Positive for at least one of the following autoantibodies: antinuclear antibodies (ANA) at a titer of ≥ 1:80, or anti-dsDNA (≥ 30 IU/mL) or anti-Smith (> ULN), anti-histone or anti-chromatin (> ULN)
• Severe, refractory SLE

Exclusion Criteria:

-Key Exclusion Criteria-

• SLE and Autoimmunity:

  • Recurrent neuropsychiatric lupus or active, severe or unstable neuropsychiatric lupus within 2 years from screening
  • Diagnosis of drug-induced SLE rather than idiopathic SLE
  • Any acute, severe lupus-related flare during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible; thus, making the patient ineligible for CD19 CAR T therapy as judged by the Investigator or Sponsor
  • Significant, likely irreversible organ damage related to SLE (e.g., end-stage renal disease) that in the opinion of the Investigator renders CD19 CAR T cell therapy unlikely to benefit the patient
  • Diagnosis of another non-SLE autoimmune disease (e.g., dermatomyositis, polymyositis, scleroderma, rheumatoid arthritis) or overlap syndrome

• Medical History:

  • History or presence of: (Within 3 months before screening visit)

    • Clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, or stroke
    • Evidence of deep venous thrombosis or pulmonary embolism
  • History or presence of severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis
  • Clinically significant, uncontrolled heart disease not due to SLE (New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled cardiac arrhythmia, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless the patient has a pacemaker) or a recent (within 12 months of screening) cardiac event
  • Active or uncontrolled fungal, bacterial, viral (including COVID-19), or other infection requiring systemic antimicrobials for management
  • Active or latent hepatitis B or active hepatitis C
  • Human immunodeficiency virus, human T-cell leukemia virus (HTLV)-1, HTLV-2 or syphilis positive test at screening
  • History of malignant neoplasms unless disease free for at least 24 months (basal cell or squamous cell carcinoma in situ, or in situ breast cancer on hormonal therapy allowed)
  • History of heart, lung, kidney, liver transplant or hematopoietic stem cell transplant
  • Pregnancy or lactating

• Laboratory and Organ Function:

  • Left ventricular ejection fraction < 45% (or < institutes lower limit of normal) confirmed by ECHO
  • Oxygen saturation (SpO2) < 90% in the absence of oxygen support

• Medications

  • Prior treatment with anti-CD19 therapy (including bispecifics), adoptive T cell therapy or any prior gene therapy product (e.g., CAR T cell therapy)
  • Immunization with a live or attenuated vaccine within 2 months of leukapheresis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AUTO1	Biological: Obecabtagene autoleucel (obe-cel); Following pre-conditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with a single dose of obe-cel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicities	Percentage of patients receiving obe-cel who experience dose-limiting toxicities (DLTs)	Up to 28 days from obe-cel infusion
Adverse events	Adverse event (AE) type, frequency, severity, and relationship with obe-cel and lymphodepletion of AEs	Up to Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission rate according to Definition of Remission in SLE (DORIS)	Remission rate as specified by Definition of Remission in SLE (DORIS)	Up to Month 12
Response over time according to Definition of Remission in SLE (DORIS)	Response over time as specified by Definition of Remission in SLE (DORIS)	Up to Month 12
Time to response according to Definition of Remission in SLE (DORIS)	Time to response as specified by Definition of Remission in SLE (DORIS)	Up to Month 12
Change over time in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)	Change compared to baseline in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score. The total score is the sum of all marked SLE-related descriptors. A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity.	Up to Month 12
Change over time in Physician's global assessment (PGA)	Change compared to baseline in physician's global assessment (PGA) of average SLE disease severity on a visual analog scale (VAS) between 0 and 3 where 0 represents no disease, 1 represents mild disease activity, 2 represents moderate disease activity, and 3 represents a severe disease activity (highest and most severe possible disease activity). At least 10% change improvement or worsening in PGA to be clinically significant compared to baseline	Up to Month 12
Pharmacokinetics (maximum serum concentration [Cmax]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood	Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion	Pre-infusion at Day -6, and at 9 timepoints post infusion between Days 1 and 28, followed by Month 2, Month 3 then 3 monthly to Month 12 and finally 6 monthly through study completion, up to a total of 3 years
Pharmacokinetics (time to reaching maximum serum concentration [Tmax]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood	Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion	Pre-infusion at Day -6, and at 9 timepoints post infusion between Days 1 and 28, followed by Month 2, Month 3 then 3 monthly to Month 12 and finally 6 monthly through study completion, up to a total of 3 years
Pharmacokinetics (area under the curve [AUC]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood	Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion	Pre-infusion at Day -6, and at 9 timepoints post infusion between Days 1 and 28, followed by Month 2, Month 3 then 3 monthly to Month 12 and finally 6 monthly through study completion, up to a total of 3 years
Pharmacokinetics (last observed quantifiable concentration [Clast]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood	Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion	Pre-infusion at Day -6, and at 9 timepoints post infusion between Days 1 and 28, followed by Month 2, Month 3 then 3 monthly to Month 12 and finally 6 monthly through study completion, up to a total of 3 years
Pharmacokinetics (time to reach last observed quantifiable concentration [Tlast]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood	Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion	Pre-infusion at Day -6, and at 9 timepoints post infusion between Days 1 and 28, followed by Month 2, Month 3 then 3 monthly to Month 12 and finally 6 monthly through study completion, up to a total of 3 years
Pharmacodynamics: B cell aplasia	Depletion of circulating B cells in the peripheral blood	Screening, pre-infusion Day -6, Day 1, Day 3, Day 28, Month 2, Month 3, Month 4, Month 6, Month 9, Month 12 then 6 monthly through study completion, up to a total of 3 years

Collaborators and Investigators

• Sponsor: Autolus Limited

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2024
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: March 25, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: CAR-T; AUTO1; Obecabtagene autoleucel (obe-cel); CD19-positive chimeric antigen receptor T cell
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: AUTO1-SL1; 2023-508236-60-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No